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Master's Dissertation
DOI
10.11606/D.5.2008.tde-28052008-145254
Document
Author
Full name
Flávia Gomes Machado
E-mail
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2008
Supervisor
Committee
Fujihara, Clarice Kazue (President)
Coimbra, Terezila Machado
Noronha, Irene de Lourdes
Title in Portuguese
Mecanismos de lesão renal progressiva decorrente do tratamento com losartan durante a lactação
Keywords in Portuguese
Hipertensão renal
Inflamação
Insuficiência renal crônica
Modelos animais
Rim/lesões
Sistema renina-angiotensina
Abstract in Portuguese
A inibição do sistema renina-angiotensina durante a lactação acarreta alterações estruturais renais irreversíveis. No presente estudo investigamos a evolução e os mecanismos envolvidos na doença renal crônica causada pela administração de losartan (L) durante a lactação. Ratos Munich-Wistar machos recém-nascidos foram divididos em dois Grupos: C, cujas mães receberam água; e LRN, cujas mães receberam L 250mg/kg/dia durante a lactação. Após 3 meses de vida, os animais LRN apresentaram redução no número de néfrons e no ritmo de filtração glomerular. Embora fossem normotensos, esses animais apresentaram hipertensão glomerular e disfunção podocitária, em consistência com a presença de albuminúria. Os estudos morfológicos mostraram que os ratos LRN apresentaram glomérulos com volumes variados, com lesões glomerulares discretas e lesões intersticiais acompanhadas de inflamação. Aos 10 meses de vida, os animais LRN apresentaram albuminúria maciça, hipertensão sistêmica, inflamação renal e progressão das lesões glomerulares e intersticiais. No presente estudo concluímos que: 1) O bloqueio do receptor AT1 durante a lactação constitui um modelo simples e reprodutível de nefropatia progressiva, que evolui sem hipertensão arterial até fases avançadas; 2) Os mecanismos envolvidos na progressão da lesão renal no modelo de LRN são semelhantes aos de outros modelos de doença renal crônica.
Title in English
Mechanisms of progressive renal injury in adult rats treated with losartan during lactation.
Keywords in English
Hypertension renal
Inflammation
Kidney/injuries
Models animal
Renal insufficiency chronic
Renin-angiotensin system
Abstract in English
Inhibition of the renin-angiotensin system during lactation causes irreversible renal structural changes. In this study we investigated the evolution and the mechanisms underlying the chronic kidney disease caused by losartan (L) administration during lactation. Male Munich-Wistar pups were divided into two Groups: C, whose dams received pure water; and LRN, whose dams received L 250 mg/kg/day. At three months of life, LRN rats showed reduced nephron number and glomerular filtration rate. Though normotensive, these animals exhibited glomerular hypertension and podocyte dysfunction, in consistency with the presence of albuminura. Morphologic studies revealed that LRN rats exhibit a wide variation of glomerular volumes, with modest glomerular injury and interstitial lesions accompanied by renal inflammation. At 10 months of age, LRN rats exhibited heavy albuminuria, systemic hypertension, renal inflammation and progression of the glomerular and interstitial lesions. Conclusions: 1) AT1 receptor blockade during lactation constitutes a simple and reproductive model of progressive nephropathy, which develops until advanced stages without arterial hypertension; 2) The mechanisms involved in the progression of renal injury in this model are similar to those implicated in other models of chronic renal disease.
 
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Publishing Date
2008-06-11
 
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